Cannabidiol (CBD) has gained much attention in the past several years for its therapeutic potential in the treatment of drugresistant epilepsy, such as Dravet syndrome. Although CBD has shown anecdotal efficacy in reducing seizure frequency, little is known regarding the potential adverse side effects of CBD on physiology, development, organogenesis, or behavior. The goal of this project was to compare the relative morphological, behavioral, and gene expression phenotypes resulting after a developmental exposure to D 9 -tetrahydrocannabinol (THC) or CBD. Zebrafish were exposed from blastula through larval stage (96 h postfertilization [hpf]) to 0.3, 0.6, 1.25, 2.5, 5 mg/l (1, 2, 4, 8, 16 mM) THC or 0.07, 0.1, 0.3, 0.6, 1.25 mg/l CBD (0.25, 0.5, 1, 2, 4 mM). Despite the similarity in THC and CBD dysmorphologies, ie, edemas, curved axis, eye/snout/jaw/trunk/ fin deformities, swim bladder distention, and behavioral abnormalities, the LC 50 for CBD (0.53 mg/l) was nearly 7 times lower than THC (3.65 mg/l). At 96 hpf, c-fos, dazl, and vasa were differentially expressed following THC exposure, but only c-fos expression was significantly increased by CBD. Cannabidiol was more bioconcentrated compared with THC despite higher THC water concentrations. This work supports the potential for persistent developmental impacts of cannabinoid exposure, but more studies are needed to assess latent effects and their molecular mechanisms of toxicity.

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Oyster reefs are vital to estuarine health, but they experience multiple stressors and globally declining populations. This study examined effects of hypoxia and tributyltin (TBT) on adult Eastern oysters (Crassostrea virginica) exposed either in the laboratory or the field following a natural hypoxic event. In the laboratory, oysters were exposed to either hypoxia followed by a recovery period, or to hypoxia combined with TBT. mRNA expression of HIF1-α and Tβ-4 along with hemocyte counts, biomarkers of hypoxic stress and immune health, respectively, were measured. In field-deployed oysters, HIF1-α and Tβ-4 expression increased, while no effect on hemocytes was observed. In contrast, after 6 and 8 days of laboratory-based hypoxia exposure, both Tβ-4 expression and hemocyte counts declined. After 8 days of exposure to hypoxia + TBT, oysters substantially up-regulated HIF1-α and down-regulated Tβ-4, although hemocyte counts were unaffected. Results suggest that hypoxic exposure induces immunosuppression which could increase vulnerability to pathogens. Oysters are important ecosystem engineers, providing essential fish habitats that are vital to the health of many estuarine ecosystems worldwide 1, 2. Oyster reefs provide numerous critical ecosystem services, including enhancing biodiversity, improving water quality, serving as nursery habitat for commercially important fisheries, stabilizing shorelines, and providing a significant economic resource for coastal communities 2-6. Despite their ecological and economic importance, it is estimated that oyster populations have suffered losses of approximately 85% worldwide in recent years, classifying oyster reefs as one of the most heavily impacted ecosystems in the world 3. Extensive restoration efforts are currently underway to restore oyster reefs in the Gulf of Mexico and other areas of the United States, where these ecosystems once flourished. However, the success of these restoration efforts has lagged far behind that of other estuarine ecosystems 7. Historically, overharvesting played a significant role in the decline of oyster populations 8 , but oyster reef recovery and resilience are also limited by poor water quality, disease, and predation 9,10. In addition, environmental contaminants (e.g., metals, pharmaceuticals, agricultural runoff) have the potential to bioaccumulate in these filter-feeding organisms 11,12. Due to their proximity to land and sources of freshwater, estuaries often experience large fluctuations in environmental conditions, such as temperature, salinity, and dissolved oxygen (DO), that can have negative short-term impacts on oyster reefs 13. The complexity of estuarine systems may result in oysters often facing combinations of stressors simultaneously, and these can have greater detrimental effects than each stressor independently 13,14. Therefore, understanding the impacts of multiple stressors, both alone and in combination, is essential to determine their impacts on aquatic organisms.